Abstract
Amphipathic copolymers such as poly(styrene-maleic acid) (SMA) are promising tools for the facile
extraction of membrane proteins (MPs) into native nanodiscs. Here, we designed and synthesized a
library of well-defined alternating copolymers of SMA analogues in order to elucidate polymer
properties that are important for MP solubilization and stability. MP extraction efficiency was
determined using KcsA from E.coli membranes and general solubilization efficiency was investigated
via turbidimetry experiments on membranes of E.coli, yeast mitochondria and synthetic lipids.
Remarkably, halogenation of SMA copolymers dramatically improved solubilization efficiency in all
systems, while substituents on the copolymer backbone improved resistance to Ca2+. Relevant
polymer properties were found to include hydrophobic balance, size and positioning of substituents,
rigidity and electronic effects. The library thus contributes to the rational design of copolymers for the
study of MPs.
Supplementary materials
Title
SI - SMA Analogues
Description
Supporting Information - Synthesis and Evaluation of a Library of Alternating Amphipathic Copolymers to Solubilize and Study Membrane Proteins
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